Back to resultsPhase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
Primary Purpose
Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Montelukast added to Hydroxyurea
Placebo added to Hydroxyurea
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
Eligibility Criteria
Inclusion Criteria:
- 1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis
- 2)Males and females age 16 years to 70 years old
- 3)Greater than 2 episodes of pain in the last 12 months
- 4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin
Exclusion Criteria:
- Judged not likely to be study compliant by his/her hematologist
- History of adverse reaction to montelukast or any of the components of montelukast
- Have used medications known to interact with montelukast such as rifampin, phenobarbital, and gemfibrozil within 4 weeks of enrollment
- Currently being treated with a leukotriene antagonist (montelukast or zileuton) or have used montelukast/zileuton within the last 60 days
- Chronic blood transfusion therapy defined as regularly scheduled transfusions.
- Hemoglobin A greater than15% on hemoglobin analysis
- Individuals with a current physician diagnosis of asthma (within last 12 months) or requires continuous supplemental oxygen, or predicted or current use of asthma medications (inhaled corticosteroids, but participants taking bronchodilators will be allowed to participate).
- Current participation in another therapeutic trial for SCD
- Known current pregnancy
- Known history of HIV
- Serum creatinine greater than 3 times the site's upper limit of normal
Sites / Locations
- Vanderbilt University Medical Center
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Montelukast added to Hydroxyurea
Placebo added to Hydroxyurea
Arm Description
Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment
Oral placebo taken daily for eight weeks with current hydroxyurea regiment
Outcomes
Primary Outcome Measures
Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)
The primary outcome measure is based on a 30% reduction, which would be ~106 ng/ml reduction. The study was designed with 25 in each group in order to explore all three aims and potential confounders. However, if the investigators are not able to accrue 25 subjects in each arm, the investigators would still be able to detect a 30% difference in sVCAM with 17 subjects in each group. The 95% confidence interval for detecting a 30% difference is between 204 ng/ml and 290 ng/ml (or an 18-42% reduction in sVCAM). Importantly, the lower limit of the 95% confidence interval (18%) is still a clinically relevant reduction in sVCAM. Thus, if the investigators detect a 30% or larger difference in sVCAM in this study, the investigators will be assured that, based on the 95% confidence interval, these data are clinically important.
Secondary Outcome Measures
Full Information
NCT ID
NCT01960413
First Posted
October 8, 2013
Last Updated
March 7, 2019
Sponsor
Vanderbilt University Medical Center
Collaborators
Medical College of Wisconsin, Versiti
1. Study Identification
Unique Protocol Identification Number
NCT01960413
Brief Title
Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
Official Title
Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia (Also Known as the Montelukast Trial in Sickle Cell Anemia)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
Medical College of Wisconsin, Versiti
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this feasibility trial, the investigators will compare participants treated with montelukast and hydroxyurea to those treated with placebo and hydroxyurea for a total of 8 weeks.
Detailed Description
The primary hypothesis for this trial is that montelukast adds efficacy to hydroxyurea therapy for improving vaso-occlusion when compared to hydroxyurea alone. The following specific aims will be tested in adolescents and adults with sickle cell disease (SCD):
Aim 1. To determine whether montelukast versus placebo added to hydroxyurea will improve markers of vaso-occlusion-associated tissue injury in adolescents and adults with sickle cell disease.
Aim 2. To evaluate physiologic effects of montelukast versus placebo added to hydroxyurea in adolescents and adults with sickle cell disease.
Subaim 2A. To determine if montelukast versus placebo added to hydroxyurea will improve lung function in adolescents and adults with sickle cell disease.
Subaim 2B. To determine if montelukast versus placebo added to hydroxyurea will improve forearm microvascular blood flow in adolescents and adults with sickle cell disease, respectively.
Funding Source - FDA OOPD
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Montelukast added to Hydroxyurea
Arm Type
Experimental
Arm Description
Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment
Arm Title
Placebo added to Hydroxyurea
Arm Type
Placebo Comparator
Arm Description
Oral placebo taken daily for eight weeks with current hydroxyurea regiment
Intervention Type
Drug
Intervention Name(s)
Montelukast added to Hydroxyurea
Intervention Type
Drug
Intervention Name(s)
Placebo added to Hydroxyurea
Primary Outcome Measure Information:
Title
Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)
Description
The primary outcome measure is based on a 30% reduction, which would be ~106 ng/ml reduction. The study was designed with 25 in each group in order to explore all three aims and potential confounders. However, if the investigators are not able to accrue 25 subjects in each arm, the investigators would still be able to detect a 30% difference in sVCAM with 17 subjects in each group. The 95% confidence interval for detecting a 30% difference is between 204 ng/ml and 290 ng/ml (or an 18-42% reduction in sVCAM). Importantly, the lower limit of the 95% confidence interval (18%) is still a clinically relevant reduction in sVCAM. Thus, if the investigators detect a 30% or larger difference in sVCAM in this study, the investigators will be assured that, based on the 95% confidence interval, these data are clinically important.
Time Frame
baseline to eight weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis
2)Males and females age 16 years to 70 years old
3)Greater than 2 episodes of pain in the last 12 months
4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin
Exclusion Criteria:
Judged not likely to be study compliant by his/her hematologist
History of adverse reaction to montelukast or any of the components of montelukast
Have used medications known to interact with montelukast such as rifampin, phenobarbital, and gemfibrozil within 4 weeks of enrollment
Currently being treated with a leukotriene antagonist (montelukast or zileuton) or have used montelukast/zileuton within the last 60 days
Chronic blood transfusion therapy defined as regularly scheduled transfusions.
Hemoglobin A greater than15% on hemoglobin analysis
Individuals with a current physician diagnosis of asthma (within last 12 months) or requires continuous supplemental oxygen, or predicted or current use of asthma medications (inhaled corticosteroids, but participants taking bronchodilators will be allowed to participate).
Current participation in another therapeutic trial for SCD
Known current pregnancy
Known history of HIV
Serum creatinine greater than 3 times the site's upper limit of normal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael R. DeBaun, MD, MPH
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joshua Field, MD, MS
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-9000
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices)
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication
IPD Sharing Access Criteria
Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
Citations:
PubMed Identifier
32208487
Citation
Field JJ, Kassim A, Brandow A, Embury SH, Matsui N, Wilkerson K, Bryant V, Zhang L, Simpson P, DeBaun MR. Phase 2 trial of montelukast for prevention of pain in sickle cell disease. Blood Adv. 2020 Mar 24;4(6):1159-1165. doi: 10.1182/bloodadvances.2019001165.
Results Reference
derived
Learn more about this trial
Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
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